Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
Sci Rep. 2018 Apr 16;8(1):6031. doi: 10.1038/s41598-018-24500-1.
The Hepatitis Delta Virus (HDV) relies mainly on host proteins for its replication. We previously identified that PSF and p54nrb associate with the HDV RNA genome during viral replication. Together with PSP1, these proteins are part of paraspeckles, which are subnuclear bodies nucleated by the long non-coding RNA NEAT1. In this work, we established the requirement for PSF, p54nrb and PSP1 in HDV replication using RNAi-mediated knockdown in HEK-293 cells replicating the HDV RNA genome. We determined that HDV replication induces the delocalization of PSP1 to cytoplasmic foci containing PABP and increases NEAT1 level causing an enlargement of NEAT1 foci. Overall, our data support a role for the main paraspeckles proteins in HDV life cycle and indicate that HDV replication causes a cellular stress and induces both a delocalization of the PSP1 to the cytoplasm and a disruption of paraspeckles.
乙型肝炎病毒 (HDV) 主要依赖宿主蛋白进行复制。我们之前发现 PSF 和 p54nrb 在病毒复制过程中与 HDV RNA 基因组结合。这些蛋白与 PSP1 一起，是由长链非编码 RNA NEAT1 引发的核周体的一部分。在这项工作中，我们使用 RNAi 介导的 HEK-293 细胞中 HDV RNA 基因组的复制来建立 PSF、p54nrb 和 PSP1 在 HDV 复制中的必要性。我们确定 HDV 复制诱导 PSP1 向含有 PABP 的细胞质焦点的去定位，并增加 NEAT1 水平，导致 NEAT1 焦点的扩大。总的来说，我们的数据支持主要核周体蛋白在 HDV 生命周期中的作用，并表明 HDV 复制会导致细胞应激，并诱导 PSP1 向细胞质的去定位和核周体的破坏。
